Browse
Submit Data
Databases
API
Help

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mesenchymal stem cell therapy for acute respiratory distress syndrome: from basic to clinics.

ABSTRACT: The 2019 novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has occurred in China and around the world. SARS-CoV-2-infected patients with severe pneumonia rapidly develop acute respiratory distress syndrome (ARDS) and die of multiple organ failure. Despite advances in supportive care approaches, ARDS is still associated with high mortality and morbidity. Mesenchymal stem cell (MSC)-based therapy may be an potential alternative strategy for treating ARDS by targeting the various pathophysiological events of ARDS. By releasing a variety of paracrine factors and extracellular vesicles, MSC can exert anti-inflammatory, anti-apoptotic, anti-microbial, and pro-angiogenic effects, promote bacterial and alveolar fluid clearance, disrupt the pulmonary endothelial and epithelial cell damage, eventually avoiding the lung and distal organ injuries to rescue patients with ARDS. An increasing number of experimental animal studies and early clinical studies verify the safety and efficacy of MSC therapy in ARDS. Since low cell engraftment and survival in lung limit MSC therapeutic potentials, several strategies have been developed to enhance their engraftment in the lung and their intrinsic, therapeutic properties. Here, we provide a comprehensive review of the mechanisms and optimization of MSC therapy in ARDS and highlighted the potentials and possible barriers of MSC therapy for COVID-19 patients with ARDS.

SUBMITTER: Qin H

PROVIDER: S-EPMC7282699 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Genetically modified mesenchymal stem cell therapy for acute respiratory distress syndrome.

Project description:Acute respiratory distress syndrome (ARDS) is a devastating hypoxemic respiratory failure, characterized by disruption of the alveolar-capillary membrane barrier. Current management for ARDS remains supportive, including lung-protective ventilation and a conservative fluid strategy. Mesenchymal stem cells (MSCs) have emerged as a potentially attractive candidate for the management of ARDS through facilitating lung tissue regeneration and repair by releasing paracrine soluble factors. Over the last decade, a variety of strategies have emerged to optimize MSC-based therapy. Among these, the strategy using genetically modified MSCs has received increased attention recently due to its distinct advantage, in conferring incremental migratory capacity and, enhancing the anti-inflammatory, immunomodulatory, angiogenic, and antifibrotic effects of these cells in numerous preclinical ARDS models, which may in turn provide additional benefits in the management of ARDS. Here, we provide an overview of recent studies testing the efficacy of genetically modified MSCs using preclinical models of ARDS.

| S-EPMC6915956 | biostudies-literature

Cell therapy in acute respiratory distress syndrome.

Project description:Acute respiratory distress syndrome (ARDS) is driven by a severe pro-inflammatory response resulting in lung damage, impaired gas exchange and severe respiratory failure. There is no specific treatment that effectively improves outcome in ARDS. However, in recent years, cell therapy has shown great promise in preclinical ARDS studies. A wide range of cells have been identified as potential candidates for use, among these are mesenchymal stromal cells (MSCs), which are adult multi-lineage cells that can modulate the immune response and enhance repair of damaged tissue. The therapeutic potential of MSC therapy for sepsis and ARDS has been demonstrated in multiple in vivo models. The therapeutic effect of these cells seems to be due to two different mechanisms; direct cellular interaction, and paracrine release of different soluble products such as extracellular vesicles (EVs)/exosomes. Different approaches have also been studied to enhance the therapeutic effect of these cells, such as the over-expression of anti-inflammatory or pro-reparative molecules. Several clinical trials (phase I and II) have already shown safety of MSCs in ARDS and other diseases. However, several translational issues still need to be addressed, such as the large-scale production of cells, and their potentiality and variability, before the therapeutic potential of stem cells therapies can be realized.

| S-EPMC6196176 | biostudies-literature

Mesenchymal stem cell-derived extracellular vesicles for the treatment of acute respiratory distress syndrome.

Project description:Acute respiratory distress syndrome (ARDS) is a serious and potentially fatal acute inflammatory lung condition which currently has no specific treatments targeting its pathophysiology. However, mesenchymal stem cells have been shown to have very promising therapeutic potential, and recently, it has been established that their effect is largely due to the transfer of extracellular vesicles (EVs). EVs have been shown to transfer a variety of substances such as mRNA, miRNA, and even organelles such as mitochondria in order to ameliorate ARDS in preclinical models. In addition, the fact that they have been proven to have the same effect as their parent cells combined with their numerous advantages over whole cell administration means that they are a promising candidate for clinical application that merits further research.

| S-EPMC6954712 | biostudies-literature

Mesenchymal stromal cell therapy for acute respiratory distress syndrome due to coronavirus disease 2019.

Project description:Background aimsThe acute respiratory distress syndrome (ARDS) resulting from coronavirus disease 2019 (COVID-19) is associated with a massive release of inflammatory cytokines and high mortality. Mesenchymal stromal cells (MSCs) have anti-inflammatory properties and have shown activity in treating acute lung injury. Here the authors report a case series of 11 patients with COVID-19-associated ARDS (CARDS) requiring mechanical ventilation who were treated with remestemcel-L, an allogeneic MSC product, under individual patient emergency investigational new drug applications.MethodsPatients were eligible if they were mechanically ventilated for less than 72 h prior to the first infusion. Patients with pre-existing lung disease requiring supplemental oxygen or severe liver or kidney injury were excluded. Each patient received two infusions of remestemcel-L at a dose of 2 million cells/kg per infusion given 48-120 h apart.ResultsRemestemcel-L infusions were well tolerated in all 11 patients. At the end of the 28-day follow-up period, 10 (91%, 95% confidence interval [CI], 59-100%) patients were extubated, nine (82%, 95% CI, 48-97%) patients remained liberated from mechanical ventilation and were discharged from the intensive care unit and two (18%, 95 CI%, 2-52%) patients died. The median time to extubation was 10 days. Eight (73%, 95% CI, 34-100%) patients were discharged from the hospital. C-reactive protein levels significantly declined within 5 days of MSC infusion.ConclusionsThe authors demonstrate in this case series that remestemcel-L infusions to treat moderate to severe CARDS were safe and well tolerated and resulted in improved clinical outcomes.

| S-EPMC8995321 | biostudies-literature

Personalized serum proteome profiles of COVID-19-associated acute respiratory distress syndrome in response to mesenchymal stem cell therapy

Project description:Five COVID-19-related ARDS patients who consented to compassionate placenta-derived (pc)-MSC treatment were followed for clinical response and disease progression. Serum samples were collected before and after pc-MSC infusion for quantitative proteomics analysis.

2023-07-13 | PXD043740 | JPOST Repository

Mesenchymal stem cells as living anti-inflammatory therapy for COVID-19 related acute respiratory distress syndrome.

Project description:Coronavirus disease 2019 (COVID-19), a pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), is growing at an exponential rate worldwide. Manifestations of this disease are heterogeneous; however, advanced cases often exhibit various acute respiratory distress syndrome-like symptoms, systemic inflammatory reactions, coagulopathy, and organ involvements. A common theme in advanced COVID-19 is unrestrained immune activation, classically referred to as a "cytokine storm", as well as deficiencies in immune regulatory mechanisms such as T regulatory cells. While mesenchymal stem cells (MSCs) themselves are objects of cytokine regulation, they can secrete cytokines to modulate immune cells by inducing anti-inflammatory regulatory Treg cells, macrophages and neutrophils; and by reducing the activation of T and B cells, dendritic and nature killer cells. Consequently, they have therapeutic potential for treating severe cases of COVID-19. Here we discuss the unique ability of MSCs, to act as a "living anti-inflammatory", which can "rebalance" the cytokine/immune responses to restore equilibrium. We also discuss current MSC trials and present different concepts for optimization of MSC therapy in patients with COVID-19 acute respiratory distress syndrome.

| S-EPMC7596438 | biostudies-literature

Mesenchymal Stem Cell-Based Therapy as an Alternative to the Treatment of Acute Respiratory Distress Syndrome: Current Evidence and Future Perspectives.

Project description:Acute respiratory distress syndrome (ARDS) represents a current challenge for medicine due to its incidence, morbidity and mortality and, also, the absence of an optimal treatment. The COVID-19 outbreak only increased the urgent demand for an affordable, safe and effective treatment for this process. Early clinical trials suggest the therapeutic usefulness of mesenchymal stem cells (MSCs) in acute lung injury (ALI) and ARDS. MSC-based therapies show antimicrobial, anti-inflammatory, regenerative, angiogenic, antifibrotic, anti-oxidative stress and anti-apoptotic actions, which can thwart the physiopathological mechanisms engaged in ARDS. In addition, MSC secretome and their derived products, especially exosomes, may reproduce the therapeutic effects of MSC in lung injury. This last strategy of treatment could avoid several safety issues potentially associated with the transplantation of living and proliferative cell populations and may be formulated in different forms. However, the following diverse limitations must be addressed: (i) selection of the optimal MSC, bearing in mind both the heterogeneity among donors and across different histological origins, (ii) massive obtention of these biological products through genetic manipulations of the most appropriate MSC, (iii) bioreactors that allow their growth in 3D, (iv) ideal culture conditions and (v) adequate functional testing of these obtaining biological products before their clinical application.

| S-EPMC8346146 | biostudies-literature

Gene Therapy for Acute Respiratory Distress Syndrome.

Project description:Acute respiratory distress syndrome (ARDS) is a devastating clinical syndrome that leads to acute respiratory failure and accounts for over 70,000 deaths per year in the United States alone, even prior to the COVID-19 pandemic. While its molecular details have been teased apart and its pathophysiology largely established over the past 30 years, relatively few pharmacological advances in treatment have been made based on this knowledge. Indeed, mortality remains very close to what it was 30 years ago. As an alternative to traditional pharmacological approaches, gene therapy offers a highly controlled and targeted strategy to treat the disease at the molecular level. Although there is no single gene or combination of genes responsible for ARDS, there are a number of genes that can be targeted for upregulation or downregulation that could alleviate many of the symptoms and address the underlying mechanisms of this syndrome. This review will focus on the pathophysiology of ARDS and how gene therapy has been used for prevention and treatment. Strategies for gene delivery to the lung, such as barriers encountered during gene transfer, specific classes of genes that have been targeted, and the outcomes of these approaches on ARDS pathogenesis and resolution will be discussed.

| S-EPMC8801611 | biostudies-literature

Corticosteroid therapy in acute respiratory distress syndrome.

Project description: Not available

| S-EPMC3576439 | biostudies-literature

Cell therapy for acute respiratory distress syndrome patients: the START study.

Project description: Not available

| S-EPMC6560575 | biostudies-literature